Exploring Small‐Molecule Modulators of Precursor miRNA Processing Associated With Glycolysis

MicroRNAs (miRNAs) are single‐stranded noncoding RNAs with 17–25 nucleotides in length that modulate gene expression by binding to specific mRNAs. They play a critical role in the maintenance and regulation of various physiological functions. In humans, approximately 2000 miRNAs have been identified, and they are predicted to regulate the expression of approximately 60% of all protein‐coding genes. Given their broad regulatory role, small molecules targeting miRNA biogenesis can induce significant changes in cellular function. In this study, we conducted a high‐throughput screening of a chemical library comprising 2320 known compounds to identify small‐molecule binders to target precursor miRNAs (pre‐miRNAs) using a fluorescent indicator displacement (FID) assay. Two sequential screenings using distinct fluorescent indicators identified 34 candidate compounds capable of interacting with the target pre‐miRNAs. The binding of these candidate compounds to the target pre‐miRNAs was further evaluated by surface plasmon resonance (SPR) analysis. We subsequently evaluated the effects of the candidate compounds on the Dicer‐mediated processing of the target pre‐miRNAs, leading to the identification of several compounds with the inhibitory effect.